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The structure of the mouse serotonin 5-HT3 receptor in lipid vesicles

Item Type:Article
Title:The structure of the mouse serotonin 5-HT3 receptor in lipid vesicles
Creators Name:Kudryashev, M. and Castaño-Díez, D. and Deluz, C. and Hassaine, G. and Grasso, L. and Graf-Meyer, A. and Vogel, H. and Stahlberg, H.
Abstract:The function of membrane proteins is best understood if their structure in the lipid membrane is known. Here, we determined the structure of the mouse serotonin 5-HT(3) receptor inserted in lipid bilayers to a resolution of 12 Å without stabilizing antibodies by cryo electron tomography and subtomogram averaging. The reconstruction reveals protein secondary structure elements in the transmembrane region, the extracellular pore, and the transmembrane channel pathway, showing an overall similarity to the available X-ray model of the truncated 5-HT3 receptor determined in the presence of a stabilizing nanobody. Structural analysis of the 5-HT3 receptor embedded in a lipid bilayer allowed the position of the membrane to be determined. Interactions between the densely packed receptors in lipids were visualized, revealing that the interactions were maintained by the short horizontal helices. In combination with methodological improvements, our approach enables the structural analysis of membrane proteins in response to voltage and ligand gating.
Keywords:5-HT3 Serotonin Receptors, Amino Acid Sequence, Lipid Bilayers, Liposomes, Molecular Dynamics Simulation, Molecular Sequence Data, Phospholipids, Protein Multimerization, Tertiary Protein Structure, Animals, Mice
Publisher:Cell Press
Page Range:165-170
Date:5 January 2016
Official Publication:https://doi.org/10.1016/j.str.2015.11.004
PubMed:View item in PubMed

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